Method of Treating Scoliosis Using a Biological Implant

ABSTRACT

The present invention is a bone growth stimulating and promoting cytokine type biological implant preferably comprising PTH coated with a controlled release biodegradable coating that is implanted preferably in the concave side of a scoliotically curved spine in combination with a bone growth inhibiting type biological implant preferably comprising methotrexate or like anti-metabolite coated with a controlled release biodegradable coating that is implanted preferably in the convex side of a scoliotically curved spine. The insertion of the biological implant is highly non-invasion, especially as compared to more conventional spine surgical methods, and the biological implant does not decrease spinal mobility or spinal range of motion.

CROSS REFERENCE TO RELATED APPLICATIONS

This nonprovisional utility application is a continuation-in-part of andclaims the benefit under 35 USC §120 to co-pending U.S. application Ser.No. 13/357,800 filed Jan. 25, 2012 and scheduled to issue as U.S. Pat.No. 8,641,738 on Feb. 4, 2014 which is a continuation-in-part of andclaims the benefit under 35 USC §120 to co-pending U.S. application Ser.No. 12/341,289 filed Dec. 22, 2008 and since issued as U.S. Pat. No.8,123,787 on Feb. 28, 2012 which claims the benefit under 35 USC §119(e)of U.S. Provisional Application No. 61/073,119, filed Jun. 17, 2008 andof U.S. Provisional Patent Application No. 61/082,503, filed Jul. 21,2008, and is a continuation-in-part of and claims the benefit under 35USC §120 to co-pending U.S. application Ser. No. 11/259,941 filed Oct.26, 2005 which claims the benefit under 35 USC §119(e) of U.S.Provisional Application No. 60/622,999, filed Oct. 28, 2004, and is acontinuation-in-part of and claims the benefit under 35 USC §120 toco-pending U.S. application Ser. No. 11/968,046 filed Dec. 31, 2007 andis a continuation of and claims the benefit under 35 USC §365(c) ofInternational Patent Application No. PCT/US2007/072785 with aninternational filing date of Jul. 3, 2007 which claims the benefit under35 USC §119(e) of U.S. Provisional Application No. 60/806,498, filedJul. 3, 2006 and of U.S. Provisional Patent Application No. 60/825,260,filed Sep. 11, 2006, all of which are incorporated, in their entirety,by this reference.

FIELD OF THE INVENTION

The present invention relates to the management of bone growth, and moreespecially management of bone growth to correct for skeletal deformitiessuch as scoliosis through the selective use of biological implants.

BACKGROUND OF THE INVENTION

Scoliosis, a medical condition in humans typically characterized by theside-to-side or lateral curvature of the spine, is a common problemaffecting more than 2 percent of the US population. Further otherrelated skeletal problems are also common in the human population. Manyinventions have been directed to therapeutics for the prevention andcorrection of scoliosis and like conditions. Such therapeutics includefor instance corrective bracing, corrective surgery and certain exerciseroutines. Certain instances of such therapeutics have shown greatereffectiveness than others. In the case of corrective surgery, suchtherapeutic may prove highly effective in correcting scoliosis buttypically is relatively invasive and potentially traumatic to thepatient, and may result in the loss of mobility and range of motion ofthe spine. Accordingly, there exists a need to for a preventative andcorrective scoliosis therapeutic that is highly minimally invasive anddoes not reduce the patient's mobility and range of motion.

SUMMARY OF THE INVENTION

The present invention therefore is a method and apparatus for bonegrowth management using biological implants. In an embodiment of theinvention, a first implant defines a bone growth stimulating andpromoting cytokine type biological implant such as Parathyroid hormone(PTH) having a controlled release or controlled time dissolvablebiodegradable coating, and a second implant defines a bone growthinhibiting type biological implant such as a composition that includesas at least a portion thereof methotrexate or like anti-metabolite andhaving a controlled release or controlled time dissolvable biodegradablecoating. The first implant is preferably inserted between vertebra, neara growth plate, on the concave side of a scoliotically curved spine bymeans of inserting the tip of a trocar into the desired area of thespine, and passing the implant through the trocar and into the desiredarea of the spine of a patient. The second implant is preferablyinserted between vertebra, near a growth plate, on the convex side of ascoliotically curved spine by means of inserting the tip of a trocarinto the desired area of the spine, and passing the implant through thetrocar and into the desired area of the spine of a patient. Afterimplant insertion and over the course of time, the implants dissolvereleasing the bone growth simulating cytokine and the bone growthinhibiting composition to the vertebra. In response, the vertebra growsa greater amount on a concave side of the spine than on a convex side ofthe spine. This asymmetric growth of the spine over time causes thespine to transition from a substantially scoliotically curvedconfiguration to a substantially non-scoliotically curved configuration.

DESCRIPTION OF DRAWINGS

In order that the advantages of the invention will be readilyunderstood, a more particular description of the invention brieflydescribed above will be rendered by reference to specific embodimentsthat are illustrated in the appended drawings. Understanding that thesedrawings depict only typical embodiments of the invention and are nottherefore to be considered to be limiting of its scope, the inventionwill be described and explained with additional specificity and detailthrough the use of the accompanying drawings, in which:

FIG. 1 is a substantially orthographic anterior/posterior schematic viewof a scoliotic spine, and;

FIG. 2 is a close-up schematic view of a portion of the spine shown inFIG. 1.

DETAILED DESCRIPTION OF THE INVENTION

Reference throughout this specification to “one embodiment,” “anembodiment,” or similar language means that a particular feature,structure, or characteristic described in connection with the embodimentis included in at least one embodiment of the present invention. Thus,appearances of the phrases “in one embodiment,” “in an embodiment,” andsimilar language throughout this specification may, but do notnecessarily, all refer to the same embodiment.

Furthermore, the described features, structures, or characteristics ofthe invention may be combined in any suitable manner in one or moreembodiments. In the following description, numerous specific details areincluded to provide a thorough understanding of embodiments of theinvention. One skilled in the relevant art will recognize, however, thatthe invention can be practiced without one or more of the specificdetails, or with other methods, components, materials, and so forth. Inother instances, well-known structures, materials, or operations are notshown or described in detail to avoid obscuring aspects of theinvention.

It is known that growth of the physeal plate results in longitudinalgrowth of long bones. In the spine, increase in height of vertebralbodies is accomplished through growth of the cartilaginous endplate.Growth of the physeal plate is influenced by both mechanical factors andsignaling molecules. Stimulation of physeal chondrocytes growth iscontrolled through a complex interaction of local and systemic pathways.Many cytokines (a category of signaling proteins) have an anaboliceffect of growth plate cartilage.

Specifically it is known that Parathyroid hormone (PTH) stimulatesphyseal chondrocytes. The overall effect of PTH on the growth platechondrocyte appears to be a stimulation of proteoglycan synthesis thatis mediated by the degradation products of membrane phosphoinositides.

It is known that Fibroblast growth factors can stimulate growth of thephyseal plate. In chick growth plate chondrocytes tritiated thymidineincorporation was increased 11-fold by fibroblast growth factor (10ng/ml) and 3.5 by TGF-beta. Studies have identified FGF18 as a selectiveligand for FGFR3 in limb bud mesenchymal cells, which suppressedproliferation and promoted their differentiation and production ofcartilage matrix. Research work has identified FGF18 and FGFR3 aspotential molecular targets for intervention in tissue engineering aimedat cartilage repair and regeneration of damaged cartilage.

Furthermore, it is know that androgens have an anabolic effect, and itis known that Insulin-like Growth Factors (IGF), Estrogens, andTransforming Growth Factors (TGF), all stimulate growth. Calciummetabolism has an influence on growth plate activity. Inorganicphosphate may act as a signaling molecule in the regulation of boneformation. All of the above listed cytokines may be incorporated in theform of a biological implant.

Furthermore, it is known that methotrexate or like anti-metabolitesfunction to inhibit bone growth. Methotrexate or like anti-metabolitemay be incorporated in the form of a biological implant.

The biological implant is preferably coated with a timed release or timedissolvable biodegradable coating. Such coatings are commerciallyavailable for instance from the SurModics Corporation and sold undervarious trademarked names such as SynBiosys, Eureka and PolyActive. Theimplant may be shaped for instance in the form of a cylinder withrounded or hemispherically shaped ends. Alternatively, the implant maybe preformed to adapt to a particular implantation target site, forinstance a surface of the implant may be shaped to form to the shape ofa portion of a vertebra. Further alternatively, the implant may besomewhat compliant so as to be at least partially pressed into a shapedthat conforms to a target site such as to the shape of a portion of avertebra.

In order to facilitate the understanding of the present invention inreviewing the drawings accompanying the specification, a feature list isprovided below. It is noted that like features are like numberedthroughout all of the figures.

FEATURE TABLE # Feature 10 Scoliotic vertebrae or spine 12 Scolioticvertebrae concave side 14 Scoliotic vertebrae convex side 20 Scolioticvertebra 22 Scoliotic vertebra concave side 24 Scoliotic vertebra convexside 30 Spinal disk 40 Biological implant - bone growth promoting 50Biological implant - bone growth inhibiting

Referring now to the drawings, the invention is a first bone growthstimulating and promoting cytokine type biological implant 40 comprisingPTH coated with a controlled release biodegradable coating that isimplanted preferably in close proximity to a concave side 12 of ascoliotically curved spine 10, and a second bone growth inhibiting typebiological implant 50 comprising a bone growth inhibiting compositionsuch as methotrexate coated with a controlled release biodegradablecoating that is implanted preferably in close proximity to a convex side14 of a scoliotically curved spine 10. More specifically, implant 40 ispreferably implanted between a concave side 22 of a first scolioticvertebra 20 and a concave side 22 of a second scoliotic vertebra 20, soas to be in near proximity to at least one growth plate of vertebra 20and so as to be in near proximity to disk 30 and implant 50 ispreferably implanted between a convex side 24 of a first scolioticvertebra 20 and a concave side 24 of a second scoliotic vertebra 20, soas to be in near proximity to at least one growth plate of vertebra 20and so as to be in near proximity to disk 30. Alternatively, it is notedhowever, that rather than both bone growth promoting implant 40 and bonegrowth inhibiting implant 50 being used in combination, bone growthpromoting implant 40 may be used without bone growth inhibiting implant50, and bone growth inhibiting implant 50 may be used without bonegrowth promoting implant 40. First biological implant 40 is preferablyinserted between a first vertebra 20 and a second vertebra 20 on concaveside 12 of scoliotically curved spine 10 by means of inserting the tipof a trocar into the desired area of concave side 12 of scolioticallycurved spine 10, and passing implant 40 through the trocar and into thedesired area of scoliotically curved spine 10 of a patient. Secondbiological implant 50 is preferably inserted between a first vertebra 20and a second vertebra 20 on convex side 14 of scoliotically curved spine10 by means of inserting the tip of a trocar into the desired area ofconvex side 14 of scoliotically curved spine 10, and passing implant 50through the trocar and into the desired area of scoliotically curvedspine 10 of a patient. Such insertion of biological implants 40 and 50is highly non-invasive, requiring only small incisions, as compared tomore conventional spine surgical methods which require large andinvasive surgical cuts. Further, the insertion of such biologicalimplants 40 and 50 does not decrease spinal mobility or spinal range ofmotion. Over the course of time, the implants 40 and 50 dissolvereleasing the bone growth simulating cytokine and/or the bone growthinhibiting anti-metabolite or functional equivalent to vertebrae 10. Inresponse to such implantation, vertebrae 10 grows a greater amount onconcave side 12 of the vertebrae 10 than on convex side 14 of vertebrae10. The asymmetric growth of vertebrae 10 over time causes vertebrae 10to transition from a substantially scoliotically curved configuration toa substantially non-scoliotically curved configuration.

It is noted that the disclosed invention is preferably practiced incombination with a screening test that screens patients for apredisposition to scoliosis, and more especially, that screens scoliosispatients for a predisposition to scoliosis curve progression. Suchscoliosis and scoliosis curve progression screening is disclosed in U.S.patent applications 60/806,498, 60/825,260, 60/825,249, 60/862,276, Ser.Nos. 11/968,046, 11/968,074, 12/024,495, and 61/082,503 the whole ofwhich are incorporated herein by reference. Such screening testsspecifically provide novel SNPs in genetic sequences involved in methodsof identifying individuals who have an altered risk of developingscoliosis or for developing a progressive scoliosis curve based on thepresence of a SNP(s) so disclosed and methods of identifying individualswho are more or less likely to respond to a treatment. Such SNPs can beassociated with either an increased or decreased likelihood or risk ofdeveloping scoliosis or scoliosis progressive. Thus the term “altered”may be used herein to encompass either of the two possibilities (e.g. anincreased or a decreased risk/likelihood). Thus by means of employingsuch screening, the method and apparatus for bone growth managementusing a biological implant as disclosed herein, is preferably onlypracticed on those patients who are determined to be at risk forscoliosis curve development or progression.

It is noted that the disclosed invention may further be practiced incombination with applying a brace to the patient. An exemplary brace forthe treatment of scoliosis preferably used in combination with themethod and apparatus for bone growth management using a biologicalimplant as disclosed herein is disclosed in U.S. patent application Ser.No. 12/145,959 which since issued as U.S. Pat. No. 7,967,767 on Jun. 28,2011, the whole of which is incorporated herein by reference.

It is noted that the disclosed invention may further be practiced incombination with preferably minimally invasive non-biological implantsfor the correction of a scoliotically curved spine. An exemplarynon-biological implant for the treatment of scoliosis preferably used incombination with the method and apparatus for bone growth managementusing a biological implant as disclosed herein is disclosed in U.S.patent application Ser. No. 11/259,941 which the current application isa continuation-in-part thereof, and the whole of which is incorporatedherein by reference.

It is noted that in an alternative to a biological implant thatcompletely dissolves over time, the implant of the present invention maybe a permanent implant. It is also noted that in an additionalembodiment, the implant may alternatively be placed on a side of thedisc or in the general vicinity of the concave or convex side of thespine.

The present invention relates to novel genetic markers associated withscoliosis, risk of developing scoliosis and risk of scoliosis curveprogression, and methods and materials for determining whether a humansubject has scoliosis, is at risk of developing scoliosis or is at riskof scoliosis curve progression.

Scoliosis in one instance refers to adolescent idiopathic scoliosis(AIS). In another instance scoliosis refers to either congenital,juvenile, syndromic or any other scoliosis condition. For the purpose ofthis invention the term scoliosis is used to describe any of theseconditions.

The contribution or association of particular SNPs and/or SNP haplotypeswith scoliosis phenotypes, such as AIS, enables the SNPs of the presentinvention to be used to develop superior diagnostic tests capable ofidentifying individuals who express a detectable trait, such asscoliosis, as the result of a specific genotype, or individuals whosegenotype places them at an increased or decreased risk of developing adetectable trait at a subsequent time as compared to individuals who donot have that genotype. For example, the presence of a single SNP knownto correlate with scoliosis might indicate an odds ratio of 1.5 that anindividual has or is at risk of developing scoliosis, whereas detectionof five SNPs, each of which correlates with scoliosis, might indicate anodds ratio of 9.5 that an individual has or is at risk of developingscoliosis. To further increase the accuracy of diagnosis orpredisposition screening, analysis of the SNPs of the present inventioncan be combined with that of other polymorphisms or other risk factorsof scoliosis, such as Cobb angle, Risser sign, gender and age.

It shall be noted that the invention disclosed herein is highly usefulin segregating and treating scoliotic patients. For instance, theinvention is useful in segregating patients into two categories, namelythose scoliotic patients whose scoliotic spine curvature will increasefrom those whose scoliotic spine curvature will not increase.Furthermore, the invention is useful in appropriately treating suchsegregated patients. For instance in patients whose scoliotic spinecurvature will increase, a therapeutic such as implanting a biologicalimplant into the patient, performing spinal surgery on the patient,applying a brace to the patient, continuing the use of a brace on thepatient, taking a spinal X-ray of the patient, continuing ongoingperiodic spinal X-rays of the patient, and monitoring spine curveprogression of the patient is administered whereas in patients whosescoliotic spine curvature will not increase, a therapeutic such as thecancelation of a contemplated implantation of a biological implant intothe patient, the cancelation of contemplated spinal surgery of thepatient, the prevention of the application of a brace to the patient,the cancelation of continued use of a brace on the patient, theprevention of the taking of a spinal X-ray of the patient, thecancelation of ongoing periodic spinal X-rays of the patient, and thecancelation of monitoring of spine curve progression of the patient isadministered.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

1. A method comprising applying at least one of a spine deformationtherapeutic and a spine non-deformation therapeutic to a patient basedon at least one spine deformation altered risk associated biologicalmarker determined to be present in the DNA of said patient.
 2. Themethod of claim 1, wherein said spine deformation therapeutic defines atleast one of implanting a biological implant into said patient,performing spinal surgery on said patient, applying a brace to saidpatient, continuing the use of a brace on said patient, taking a spinalX-ray of said patient, continuing ongoing periodic spinal X-rays of saidpatient, and monitoring spine curve progression of said patient, andwherein said spine non-deformation therapeutic defines at least one ofthe cancelation of a contemplated implantation of a biological implantinto said patient, the cancelation of contemplated spinal surgery ofsaid patient, the prevention of the application of a brace to saidpatient, the cancelation of continued use of a brace on said patient,the prevention of the taking of a spinal X-ray of said patient, thecancelation of ongoing periodic spinal X-rays of said patient, and thecancelation of monitoring of spine curve progression of said patient. 3.The method of claim 2, wherein said biological implant defines adissolvable bone growth modulator.
 4. The method of claim 3, whereinsaid biological implant defines at least one of a dissolvable bonegrowth stimulant coated with a dissolvable coating and a dissolvablebone growth inhibitor coated with a dissolvable coating.
 5. The methodof claim 4, wherein said bone growth stimulant comprises at least one ofa Parathyroid hormone, a Fibroblast growth factor, an androgen, anInsulin-like Growth Factor, an Estrogen, a Transforming Growth Factor,and an inorganic phosphate, and wherein said bone growth inhibitorcomprises methotrexate.
 6. The method of claim 2, wherein saidbiological implant defines at least one bone growth promoting implantand at least one bone growth inhibiting implant, and wherein said spineincludes a curve formed therein, and wherein said at least one bonegrowth promoting implant is inserted proximate a concave side of saidcurve of said spine, and wherein said at least one bone growthinhibiting implant is inserted proximate a convex side of said curve ofsaid spine.
 7. The method of claim 2, wherein said spinal surgerydefines joining at least one mechanical implant to a first vertebra andto a second vertebra of the spine of said patient, and wherein saidbrace defines an external brace for scoliosis therapy comprising: a rodhaving a first end and a second end; an auxiliary pad connected to saidrod proximate said first end of said rod; a pelvic mold connected tosaid rod proximate said second end of said rod; a mechanical adjustmentmechanism coupled to said rod between said first end of said rod andsaid second end of said rod, and an apical pad connected to saidadjustment mechanism.
 8. A method comprising applying at least one of aspine deformation therapeutic to a patient at increased risk of spinedeformation based on at least one spine deformation associatedbiological marker determined to be present in said patient and a spinenon-deformation therapeutic to a patient at decreased risk of spinedeformation based on at least one spine non-deformation associatedbiological marker determined to be present in said patient.
 9. Themethod of claim 8, wherein said spine deformation therapeutic defines atleast one of implanting a biological implant into said patient,performing spinal surgery on said patient, applying a brace to saidpatient, continuing the use of a brace on said patient, taking a spinalX-ray of said patient, continuing ongoing periodic spinal X-rays of saidpatient, and monitoring spine curve progression of said patient, andwherein said spine non-deformation therapeutic defines at least one ofthe cancelation of a contemplated implantation of a biological implantinto said patient, the cancelation of contemplated spinal surgery ofsaid patient, the prevention of the application of a brace to saidpatient, the cancelation of continued use of a brace on said patient,the prevention of the taking of a spinal X-ray of said patient, thecancelation of ongoing periodic spinal X-rays of said patient, and thecancelation of monitoring of spine curve progression of said patient.10. The method of claim 9, wherein said biological implant defines abone growth modulator comprising at least one of a dissolvable bonegrowth stimulant coated with a dissolvable coating and a dissolvablebone growth inhibitor coated with a dissolvable coating.
 11. The methodof claim 10, wherein said bone growth stimulant comprises at least oneof a Parathyroid hormone, a Fibroblast growth factor, an androgen, anInsulin-like Growth Factor, an Estrogen, a Transforming Growth Factor,and an inorganic phosphate, and wherein said bone growth inhibitorcomprises methotrexate.
 12. The method of claim 9, wherein saidbiological implant defines at least one bone growth promoting implantand at least one bone growth inhibiting implant, and wherein said spineincludes a curve formed therein, and wherein said at least one bonegrowth promoting implant is inserted proximate a concave side of saidcurve of said spine, and wherein said at least one bone growthinhibiting implant is inserted proximate a convex side of said curve ofsaid spine.
 13. The method of claim 9, wherein said spinal surgerydefines joining at least one mechanical implant to a first vertebra andto a second vertebra of the spine of said patient, and wherein saidbrace defines an external brace for scoliosis therapy comprising: a rodhaving a first end and a second end; an auxiliary pad connected to saidrod proximate said first end of said rod; a pelvic mold connected tosaid rod proximate said second end of said rod; a mechanical adjustmentmechanism coupled to said rod between said first end of said rod andsaid second end of said rod, and an apical pad connected to saidadjustment mechanism.
 14. A method comprising applying at least one of aspine deformation therapeutic and a spine non-deformation therapeutic toa patient based on at least one spine deformation altered riskassociated biological marker determined to be present in said patient.15. The method of claim 14, wherein said spine deformation therapeuticdefines at least one of implanting a biological implant into saidpatient, performing spinal surgery on said patient, applying a brace tosaid patient, continuing the use of a brace on said patient, taking aspinal X-ray of said patient, continuing ongoing periodic spinal X-raysof said patient, and monitoring spine curve progression of said patient,and wherein said spine non-deformation therapeutic defines at least oneof the cancelation of a contemplated implantation of a biologicalimplant into said patient, the cancelation of contemplated spinalsurgery of said patient, the prevention of the application of a brace tosaid patient, the cancelation of continued use of a brace on saidpatient, the prevention of the taking of a spinal X-ray of said patient,the cancelation of ongoing periodic spinal X-rays of said patient, andthe cancelation of monitoring of spine curve progression of saidpatient.
 16. The method of claim 15, wherein said biological implantdefines a bone growth modulator comprising at least one of a dissolvablebone growth stimulant coated with a dissolvable coating and adissolvable bone growth inhibitor coated with a dissolvable coating. 17.The method of claim 16, wherein said bone growth stimulant comprises atleast one of a Parathyroid hormone, a Fibroblast growth factor, anandrogen, an Insulin-like Growth Factor, an Estrogen, a TransformingGrowth Factor, and an inorganic phosphate, and wherein said bone growthinhibitor comprises methotrexate.
 18. The method of claim 15, whereinsaid biological implant defines at least one bone growth promotingimplant and at least one bone growth inhibiting implant, and whereinsaid spine includes a curve formed therein, and wherein said at leastone bone growth promoting implant is inserted proximate a concave sideof said curve of said spine, and wherein said at least one bone growthinhibiting implant is inserted proximate a convex side of said curve ofsaid spine.
 19. The method of claim 15, wherein said spinal surgerydefines joining at least one mechanical implant to a first vertebra andto a second vertebra of the spine of said patient, and wherein saidbrace defines an external brace for scoliosis therapy comprising: a rodhaving a first end and a second end; an auxiliary pad connected to saidrod proximate said first end of said rod; a pelvic mold connected tosaid rod proximate said second end of said rod; a mechanical adjustmentmechanism coupled to said rod between said first end of said rod andsaid second end of said rod, and an apical pad connected to saidadjustment mechanism.
 20. The method of claim 14, wherein said spinedeformation altered risk associated biological marker defines the minorallele of a SNP.